MUSCLE PHYSIOLOGY

• What percentage of body mass is skeletal muscle?

  40%
• Where does skeletal muscle arise from?

  The mesoderm (middle layers of a 3 layered disc structure in embryos) as myoblasts
• Myoblasts become myotube which mature into immature muscle fibres that continue to form and mature
• Muscle fibre formation is completed at 24 weeks gestation. Innervation begins at 10 weeks
• Muscle fibres bulk and lengthen (hypertrophy and sarcomerogenesis) after birth dependent on GF's, endocrine system, genetic expression and environment
• Functional characteristics of skeletal muscle:

  • Excitability - skeletal muscle has a resting membrane potential (RMP) allowing it to conduct action potentials
  • Contractability - ability to generate force
  • Extensibility - able to stretch whilst contracting or passively while relaxed
  • Elasticity - ability to return to resting length once distending forces are removed
• Function of skeletal muscle:

  • Movement
  • Posture and stability
  • Heat generation
  • Variable and selective force generator
• Skeletal muscle fibres are long, cylindrical, multinucleated cell of myofibrils
• Skeletal muscle fibres contain specifically arranged proteins which produce force
• Skeletal muscle fibres have limited repair by satellite cells (vital to health and repair) and belong to the motor unit
• Sarcolemma - cell membrane: Defines outer boundaries, wraps multiple myofibrils and contains innervation joints
• Myoglobin = localised oxygen store
• Glycosomes = onsite source of glycogen
• Myofibrils are repeated sarcomere units
• Sarcomere structure:

  • Z line: Boundary of each sarcomere
  • I (isotropic band): actin/thin filament only - light on xray
  • H zone: myosin/thick filament only
  • M line: myosin linked by accessory proteins
  • A (anisotropic band): actin and myosin overlap - dark on xray
• Contractile proteins – actin and myosin

  Myosin

  • Has a ‘tail’ to fix in position
  • Has a flexible neck (S2) to provide power stroke
  • Has a globular head (S1) that binds to actin and ATP; also ATPase site

  Actin

  Double helix strands

  Binding site for myosin

  Has regulatory proteins running through the helix and dotted along the surface
• Regulatory proteins - troponin and tropomyosin

  Tropomyosin

  • Associated with troponin
  • Blocks myosin binding sites so regulates actin/myosin interactions

  Troponin

  • Consists of 3 subunits
  • 1 subunit binds to Ca2+, causing tropomyosin to move and expose myosin binding sites
• Structural proteins - titin and nebulin (dystrophin, myomesin, and vimentin)

  • Titin and Nebulin - passive tension contributors
• Sliding filament theory

  • When relaxed actin and myosin overlap slightly. Actin slides
  • When fully contracted actin and myosin overlap fully
• Sarcoplasmic reticulum

  • Complex system of membrane that surrounds myofibrils
  • They uptake, store, and release CA2+ ions - when calcium is taken up by the sarcoplasmic reticulum, there is less within the interstitial fluid, creating a gradient
• Transverse (T) tubule

  • An invagination of the sarcolemma (2 per sarcolemma)
  • Penetrates the structure of a muscle fibre to make intimate contact with the sarcoplasmic reticulum
  • Release CA2+ ions
• Endomysium – delicately wraps each fibre; acts as an electrical insulator; it’s a loose CT (areolar and reticular)
• Perimysium – binds groups of fibres into functional units - fascicles; muscle spindles (proprioceptor)
• Epimysium – wraps whole muscle; tough dense irregular CT; blends with deeper layers of fascia – separates one muscle from another
• All levels of connective tissue wrapping are longitudinally continuous
• CT wrappings fuse together to form tendons
• Eccentric contraction = passive tension: more force produced by the interaction of contractile proteins (actin and myosin)
• Musculotendinous junction

  • Where muscle fibres and connective tissue fibres blend with the connective tissue of the tendon
  • Where golgi tendon organs are present
  • Tendons - dense irregular connective tissue. Transmit force generated within muscle to bone (enthesis). Can stretch and recoil
• Nerve supply

  • Afferent (sensory) e.g. proprioceptors - golgi tendons (tension) and muscle spindles (length)
  • Nociceptors - pain
  • Efferent (motor) inc. motor unit and neuromuscular junctions
• Motor unit consists of:

  • one anterior horn cell
  • one alpha motor neurone
  • axonal branches
  • innervated muscle fibres
• Motor unit characteristics

  • Muscle fibres are innervated once
  • Muscle fibres belong to one motor unit
  • Muscle fibres belonging to a motor unit will be the same muscle fibre type
  • Muscle fibres in one motor unit are activated simultaneously (all or none law)
  • Muscle fibres in a motor unit are scattered with the muscle
  • Not all the same size
  • Big motor units have large anterior horn cells associated with the large number of muscle fibres - fast twitch fibres (type II) - power
• Neuromuscular junctions - the point at which a neuron meets with the sarcolemma of a muscle

  • Acetylcholine (ACh) is stored in vesicles within the axon terminal
  • An action potential arrives at terminal and depolarises (positive charge) the presynaptic membrane
  • Calcium ions enter the terminal from external sources (sarcoplasmic reticulum)
  • The CA2+ ions cause the vesicles to migrate and fuse with the presynaptic membrane
  • Acetylcholine is released and diffused across the synapse
• Concentric contraction - at rest

  • Low CA2+ levels in sarcoplasm
  • Tropomyosin blocks myosin binding to actin
  • ADP + Pi bound to myosin head so myosin is ready for attachment (cocked) and has a high affinity for actin
• Concentric contraction - crossbridge cycling

  • Influx of calcium causes tropomyosin to expose myosin heads
  • Myosin head has high energy configuration which causes myosin cross bridge to attach to the actin myofilament
  • ADP and Pi are released causing the myosin heads to slide actin closer to the M line (myosin pivots and bends)
  • New ATP attaches to the myosin head causing it it to reattach it cross bridge as myosin head has low energy configuration
  • ATP is hydrolysed and myosin is cocked
• During contraction 50% of available cross bridges are made at any time
• Concentric contractions cause the sarcomere to shorten by 35-40%
• Eccentric contractions = lengthened sarcomere
• Increasing the rate of AP arrival increases the rate of muscle contraction.
• One AP equals a twitch.
• More APs result in wave summation, unfused tetanus, or fused tetanus.